Zhang et al. manipulated red blood cells to serve as artificial antigen-presenting cells (RCT-aAPC) expressing three signals: SIINFEKL peptide on MHC-I, 4-1BBL, and a cytokine (IL-7, IL-12, or IL-15). RCT-aAPC with IL-12 most effectively stimulated OT1 expansion and EG7.OVA tumor control in vivo, also inducing endogenous T cell activation, OT1 memory responses, and epitope spreading. RCT-aAPC distributed primarily to the spleen, colocalizing with transferred OT1 cells, and led to minimal and transient systemic toxicities. RCT-aAPC expressing gp100 or E7 could activate and expand T cells specific to these antigens.
Contributed by Alex Najibi
ABSTRACT: Checkpoint inhibitors and T-cell therapies have highlighted the critical role of T cells in anti-cancer immunity. However, limitations associated with these treatments drive the need for alternative approaches. Here, we engineer red blood cells into artificial antigen-presenting cells (aAPCs) presenting a peptide bound to the major histocompatibility complex I, the costimulatory ligand 4-1BBL, and interleukin (IL)-12. This leads to robust, antigen-specific T-cell expansion, memory formation, additional immune activation, tumor control, and antigen spreading in tumor models in vivo. The presence of 4-1BBL and IL-12 induces minimal toxicities due to restriction to the vasculature and spleen. The allogeneic aAPC, RTX-321, comprised of human leukocyte antigen-A*02:01 presenting the human papilloma virus (HPV) peptide HPV16 E7(11-19), 4-1BBL, and IL-12 on the surface, activates HPV-specific T cells and promotes effector function in vitro. Thus, RTX-321 is a potential 'off-the-shelf' in vivo cellular immunotherapy for treating HPV_+_cancers, including cervical and head/neck cancers.
Author Info: (1) Rubius Therapeutics, Inc., Cambridge, MA, USA. (2) Rubius Therapeutics, Inc., Cambridge, MA, USA. (3) Rubius Therapeutics, Inc., Cambridge, MA, USA. (4) Rubius Therapeutics, In
Author Info: (1) Rubius Therapeutics, Inc., Cambridge, MA, USA. (2) Rubius Therapeutics, Inc., Cambridge, MA, USA. (3) Rubius Therapeutics, Inc., Cambridge, MA, USA. (4) Rubius Therapeutics, Inc., Cambridge, MA, USA. (5) Rubius Therapeutics, Inc., Cambridge, MA, USA. (6) Rubius Therapeutics, Inc., Cambridge, MA, USA. (7) Rubius Therapeutics, Inc., Cambridge, MA, USA. (8) Rubius Therapeutics, Inc., Cambridge, MA, USA. (9) Rubius Therapeutics, Inc., Cambridge, MA, USA. (10) Rubius Therapeutics, Inc., Cambridge, MA, USA. (11) Rubius Therapeutics, Inc., Cambridge, MA, USA. (12) Rubius Therapeutics, Inc., Cambridge, MA, USA. (13) Rubius Therapeutics, Inc., Cambridge, MA, USA. (14) Rubius Therapeutics, Inc., Cambridge, MA, USA. (15) Rubius Therapeutics, Inc., Cambridge, MA, USA. (16) Rubius Therapeutics, Inc., Cambridge, MA, USA. (17) Rubius Therapeutics, Inc., Cambridge, MA, USA. (18) Rubius Therapeutics, Inc., Cambridge, MA, USA. (19) Rubius Therapeutics, Inc., Cambridge, MA, USA. (20) Rubius Therapeutics, Inc., Cambridge, MA, USA. (21) Rubius Therapeutics, Inc., Cambridge, MA, USA. (22) Rubius Therapeutics, Inc., Cambridge, MA, USA. tiffany.chen@rubiustx.com.
